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Supplemental digital content is available in the text., Objectives Patients are unintentionally, yet frequently, harmed in situations that are deemed preventable. Incident reporting systems help prevent harm, yet there is considerable variability in how patient safety incidents are reported. This may lead to inconsistent or unnecessary patterns of incident reporting and failures to identify serious patient safety incidents. This systematic review aims to describe international approaches in relation to defining serious reportable patient safety incidents. Methods Multiple electronic and gray literature databases were searched for articles published between 2009 and 2019. Empirical studies, reviews, national reports, and policies were included. A narrative synthesis was conducted because of study heterogeneity. Results A total of 50 articles were included. There was wide variation in the terminology used to represent serious reportable patient safety incidents. Several countries defined a specific subset of incidents, which are considered sufficiently serious, yet preventable if appropriate safety measures are taken. Terms such as “never events,” “serious reportable events,” or “always review and report” were used. The following dimensions were identified to define a serious reportable patient safety incident: (1) incidents being largely preventable; (2) having the potential for significant learning; (3) causing serious harm or have the potential to cause serious harm; (4) being identifiable, measurable, and feasible for inclusion in an incident reporting system; and (5) running the risk of recurrence. Conclusions Variations in terminology and reporting systems between countries might contribute to missed opportunities for learning. International standardized definitions and blame-free reporting systems would enable comparison and international learning to enhance patient safety.